title: Simvastatin reduces melanoma progression in a murine model.
abstract: Statins are a class of drugs that inhibit the rate-limiting step in the cholesterol biosynthetic pathway and show an anticancer effect, probably through the inhibition of cell proliferation. To date, the exact mechanism of cancer cell growth arrest induced by statins is not known. We report that simvastatin is able to induce apoptosis in melanoma cells but not in normal cells and also able to contrast the growth of tumor in an experimental melanoma murine model. We observed a delay in the tumor development in almost the 50% of the simvastatin administered animals and a strong reduction of the tumor volume with a differences of ~150% compared to the controls. Also the survival rate was significantly higher in mice that received the drug with a survival increase of ~130% compared to the controls. The tumor growth reduction in mice was supported by the results of cell migration assay, confirming that simvastatin clearly reduced cell migration. Moreover, simvastatin induced a strong downregulation of NonO gene expression, an important growth factor involved in the splicing regulation. This result could explain the decrease of melanoma cells proliferation, suggesting a possible action mechanism. The results derived from our experiments may sustain the many reports on the anticancer inhibitory property of statins and encourage new studies on this drug for a possible use in therapy, probably in combination with conventional chemotherapy.
authors.affiliation: Institute of Genetics and Biophysics A. Buzzati Traverso, CNR Naples, Naples, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Zanfardino
authors.forename: Carmine
authors.initials: C
authors.lastname: Spampanato
authors.forename: Rosanna
authors.initials: R
authors.lastname: De Cicco
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Buommino
authors.forename: Anna
authors.initials: A
authors.lastname: De Filippis
authors.forename: Salvatore
authors.initials: S
authors.lastname: Baiano
authors.forename: Adriano
authors.initials: A
authors.lastname: Barra
authors.forename: Franco
authors.initials: F
authors.lastname: Morelli
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002784:Cholesterol / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D018450:Disease Progression; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000401:mortality; D051379:Mice; D008810:Mice, Inbred C57BL; D016601:RNA-Binding Proteins; D019821:Simvastatin / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality; D013534:Survival; D015996:Survival Rate; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C500331:Nono protein, mouse; D016601:RNA-Binding Proteins; D002784:Cholesterol; D019821:Simvastatin